In 1516, when he was 64 years old, Leonardo da Vinci found himself at a crossroads. His patron, Giuliano de’ Medici, the brother of Pope Leo X, had just died and new commissions were not forthcoming in his home country. The French, however, couldn’t sing his praises loudly enough.

Leonardo da Vinci

So he packed up all his possessions for the three-month journey to Amboise, France, and a train of mules hauled his “books, scientific instruments, clothes,” and his most cherished work-in-progress, the painting that would later be known as the “Mona Lisa.”

That lengthy journey would be just the first for the iconic work, which would eventually see a life of travel and majesty far sur­passing the life of its subject, Lisa Gherardini.

In her new history, “Mona Lisa,” veteran journalist Dianne Hales shares with us the tumultuous lives of both Gherardini and the artist who immortalized her, and brings us along on the travels of a work of art for which love and esteem have increased markedly over the centuries.

Mona Lisa: A Life Discoveredby Dianne Hales(Simon & Schuster)

The woman known to us as Mona Lisa was most likely a Florentine housewife and mother of six. (“Monna,” with two n’s, is a title of respect in Italian meaning “Madame.”)

Born in 1479, she was married off at 15 to a silk merchant named Francesco del Giocondo who was “just shy of 30, a fairly typical [age] difference for an upper-class union.” (In Italy, the painting is known as “La Gioconda,” after her married name.)

There is no information on how Leonardo came to paint the Florentine housewife, but we do know that the artist’s household was just “steps” away from the home of Gherardini’s grandparents, and that da Vinci’s father did business with her husband.

We also know that the painting was underway by 1503, at which point Gherardini was a 24-year-old mother of five.

By then, Leonardo’s reputation as a genius was widespread, but he could also be seen as something of a flake. His head would be so entwined with mathematical and scientific concepts that the everyday world — including commissions he had already accepted — sometimes went by the wayside. But by immersing himself in these concepts, da Vinci was giving himself the ultimate artist’s education.

Tuscan princesses Natalia, left, and Irina Strozzi are descendants of Lisa Gherardini, the model for the Mona Lisa. In 2007, an Italian genealogy expert revealed that the Strozzi family directly descends from Gherardini.Photo: Getty Images

“Leonardo’s entire career had led him to this point — and this portrait,” writes Hales. “Through years of advanced mathematical calculations, he had worked out the perfect proportions for a human head. In experiments with optics, he had observed a pupil’s response to the play of light and shadow.”

Leonardo was so committed to artistic advancement through science that he even took to frequenting the local morgue, filled with “dead men, dismembered and flayed and terrible to behold,” so that he could sketch the corpses in order to learn the intricacies of human anatomy.

“By dissecting cadavers,” Hales writes, “he had isolated the muscles that curve a finger or draw the lips into a smile. All that 16th century science could offer would sharpen his eye and guide his hand.”

(He would do this throughout his career, only stopping when Pope Leo X himself demanded he do so after learning that Leonardo had skinned three corpses.)

Hales makes clear that when Leonardo painted Gherardini, he was attempting something the art world had never seen before.

Photo: Reuters

“Leonardo wanted to portray the complex psychological life of a real person,” says Monsignor Timothy Verdon, who teaches art in Florence through Stanford University, in the book. “He may have wanted to see the play of different feelings and responses to different stimuli on her face. The emotions, the intelligence, the obvious wit that he captured are what makes Lisa’s face so alive and so fascinating to us.”

It turns out as well that Mona Lisa’s smile, perhaps the most famous in the world, was a remarkable technical achievement.

“Most Renaissance artists, whose attempts at grins ended up looking like grimaces, viewed the smile as an elusive Holy Grail, a consummate technical challenge,” Hales writes, crediting a Florence art professor named Marco Cianchi for the information. “Leonardo himself spent years experimenting with similar expressions until, with the gentle slope of Lisa’s mouth, he elevated his skills to an incomparable new level.”

Officials gather around the Mona Lisa after it was stolen, then recovered and returned to Paris, January 4th, 1914.Photo: Getty Images

There is no hard data on when the painting was completed, although it’s clear that Leonardo worked on it for years in both Florence and Rome, continually revising and adding finer and finer brush strokes as his skill came to match his vision.

Leonardo died in 1519 and left the painting to a friend. French King Francis I bought it soon after for “a staggering sum: an estimated 12,000 francs, the equivalent of almost $10 million today.”

A history of the Mona Lisa is illustrated on the front page of a French newspaper in December 28, 1913. The art shows King Francois I purchase from da Vinci, the theif in the Lourve museum in 1911 and it’s return to Paris.Photo: Getty Images

The king hung the painting, which the French called “La Joconde,” in “his six-room bathing suite,” where decades of proximity to steam damaged it. A Dutch restorer, in an effort to repair it, applied “a thick coat of lacquer” that permanently dulled its colors.

The “Mona Lisa” was passed around by French royalty — some of whom adored it, others of whom couldn’t have cared less — an

d in the late 1700s it wound up in the court of King Louis XVI and Queen Marie Antoinette. After the French Revolution, the French people took possession of all the art in the royal palaces, but three years later Napoleon Bonaparte had the painting, which he referred to as “Madame Lisa,” brought to his bedroom.

Bonaparte would later become “infatuated with a young Italian woman who bore a remarkable resemblance to the lady in the painting.” This woman, it turned out, was Teresa Guadagni, a descendant of Gherardini’s.

The painting was sent to the Louvre in 1815, the first time that the “Mona Lisa” was available for public viewing. Over subsequent decades, copies spread around Europe just as the world was falling in love with the romance of Paris, and the “Mona Lisa” came to be seen as an object of romantic fascination.

The Louvre in 1865.Photo: Getty Images

“To the Romantics of the late 19th century, Lisa’s became the face that launched a thousand fantasies,” writes Hales. “Suitors bearing flowers, poems and impassioned notes climbed the grand staircase of the Louvre to gaze into her ‘limpid and burning eyes.’ Essayists agonized over Leonardo’s femme fatale — was she Madonna or whore? Mother or temptress?”

“Mona Lisa” had a restful century or so until Aug. 22, 1911, when it vanished from the Louvre. The theft was huge international news, coverage of which introduced the painting to many for the first time. Parisians, meanwhile, mourned as if they had lost a loved one, lining up to “view the blank space [where the painting had been].”

When a provocateur poet named Guillaume Apollinaire was arrested as a suspect, his friend Pablo Picasso was called in for questioning.

Vincenzo Peruggia who attempted to steal The Mona Lisa in 1911.Photo: Getty Images

The “Mona Lisa” was recovered, in almost perfect condition, two years later. The thief was an Italian named Vincenzo Peruggia, a handyman at the Louvre who, it turned out, carefully flinched the painting “from the frame he had helped construct.” He first claimed to have done it to return the painting to its ancestral home of Italy, but in court, other motives surfaced.

Two marry carry the painting back to the Louvre in 1914.Photo: Getty Images

“I fell victim to her smile,” he told the court. “I fell in love with her.”

The painting was taken on a brief tour of Italy, then returned to France, where “Mona Lisa” became not just a work of art, but a fashion inspiration as well.

“Society women adopted the ‘La Joconde look,’” writes Hales, “dusting yellow powder on their faces and necks to suggest her golden complexion and immobilizing their facial muscles to mimic her smile. In Parisian cabarets, dancers dressed as La Joconde performed a saucy can-can.”

While public perception of “Mona Lisa” had shifted over the centuries, the theft cemented its legend.

“Something beyond the painting’s wild popularity had changed,” writes Hales. “The ‘Mona Lisa’ had left the Louvre a work of art; she returned as a public property, the first mass art icon.”

This icon was hidden in safe houses throughout World War II, but her spirit infused the war effort, as “the British used a coded message — La Joconde garde un sourire (The ‘Mona Lisa’ keeps her smile) — to contact the French resistance.”

An employee of the Louvre rehangs the painting in October, 1947 during the re-opening of the Grand Gallery after it had been closed for two years following the end of World War II.Photo: Getty Images

With the world clamoring for a piece of this phenomenon, the sixties saw “Mona Lisa” go on tour. Protected by a $100 million insurance policy (around $608 million today), the painting was sent overseas for the first time in a “custom-made 350-pound airtight, floatable, temperature-and-humidity controlled container constructed of steel alloy and padded with Styrofoam.”

The painting was greeted in Washington, D.C. by President Kennedy, who said of it, “the life of this painting spans the entire life of the New World.” It toured again in the 1970s, this time to Tokyo, but has remained otherwise secured in the Louvre.

The French minister of Culture and his wife stand with JFK and Jackie when The Mona Lisa was on loan from France at the National Gallery in 1963.Photo: Getty Images

Today, new technology allows art researchers to learn ever more about this groundbreaking work.

Starting in 2004, the “Mona Lisa” “underwent the most extensive battery of technological examinations ever performed on a painting . . . including X-rays, infrared and multispectrum photographs and ultraviolet fluorescence scans.” The many insights — presented in detail in the 2006 book “Mona Lisa: Inside the Painting” — include how Leonardo refined the work to convey Gherardini’s beauty.

Mentioning “before” and “after” photos as revealed by the scans, Hales notes that in the “before” shot, “her face appears stolid and square, her features heavy, her cheeks thick, the grain of her skin irregular.” By the time Leonardo had finished, “Lisa’s face [had] rounded into an oval, with delicate features and gleaming skin.”

The “before” findings may support a contention held by many that da Vinci painted a second “Mona Lisa,” an earlier version that he began, painting the face and some of the body, but then had assistants complete.

Tourists crowd around the painting at the Louvre.Photo: Getty Images

This belief first went public in 1584, when an artist named Giovanni Paolo Lomazzo wrote that “the two most beautiful and important portraits by Leonardo are the ‘Mona Lisa’ and the ‘Gioconda.’”

The photo on the right is believed to be an earlier version of da Vinci’s masterpiece.Photo: Getty Images

Many art experts have seen the second painting and believe that only da Vinci could have created something so exquisite, but none have been able to definitely prove that the work is da Vinci’s.

A Swiss non-profit called the Mona Lisa Foundation was recently formed to prove the painting’s origin as a da Vinci original using the latest technology. The foundation has spent over $1 million so far, and while their efforts to date have done nothing to “disprove a Leonardo authorship,” they have not yet been able to confirm it either.

But for most, the true magic of the “Mona Lisa” comes not from an obsessive collection of historical information, but from the pure passion that viewing it inspires.

Those seeking to learn about the power and meaning of the grand Madame need only look to the tale of 19th century artist Luc Maspero.

Increasingly enthralled with the painting over time, love grew to obsession such that by 1852, he could take no more. That year, Maspero “threw himself from the fourth-floor window of his Paris hotel, leaving a note that said, ‘For years I have grappled desperately with her smile. I prefer to die.’ ”